Rh-Catalyzed Enantioselective Aryl C-H Bond Cyclopropylation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Aryl C-H bond functionalization is crucial for synthesizing complex organic molecules.
• Current methods for cyclopropanation often lack selectivity or require pre-functionalized starting materials.
• Accessing novel chemical space, particularly cyclopropanated motifs, remains a significant challenge in drug discovery and materials science.

Purpose of the Study:

• To develop a novel catalytic system for site-, regio-, diastereoselective, and enantioselective cyclopropylation of aryl C-H bonds.
• To explore the use of diazomethyl hypervalent iodine reagents and styrenes in conjunction with dirhodium carboxylate catalysts.
• To enable the efficient construction of cyclopropane rings from readily available aromatic feedstocks and drug molecules.

Main Methods:

• Utilized paddlewheel dirhodium carboxylate catalysts for aryl C-H bond cyclopropylation.
• Employed diazomethyl hypervalent iodine reagents and styrenes as key reaction components.
• Achieved catalytic generation of a chiral Rh(II) carbene intermediate via electrophilic aromatic substitution with chiral Rh(II) carbynoids.

Main Results:

• Demonstrated site-, regio-, diastereo-, and enantioselective cyclopropylation of aryl C-H bonds.
• Successfully constructed cyclopropane rings using diverse aromatic feedstocks and incorporating them into drug molecules.
• Established a new strategy for accessing previously unexplored cyclopropanated chemical space.

Conclusions:

• The developed catalytic system provides an efficient and selective method for aryl C-H bond cyclopropylation.
• This strategy significantly expands the synthetic toolkit for creating complex cyclopropanated structures.
• The approach holds promise for drug discovery and the development of novel organic materials.